OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder. METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment. CONCLUSIONS CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals ; Rats, Sprague-Dawley ; Male ; Cannabidiol/therapeutic use* ; Rats ; Circadian Rhythm/drug effects* ; Propofol/adverse effects* ; Anesthesia, General/adverse effects* ; Sleep Wake Disorders/chemically induced* ; Hypothalamus/metabolism* ; Electroencephalography

Objective:To investigate the effects of early percutaneous coronary intervention (PCI) on myocardial perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction (STEMI) after thrombolysis.Methods:A total of 108 patients with STEMI treated in the Second Hospital of Hebei Medical University from January 2020 to December 2022 were divided into early PCI following thrombolysis group ( n=65) and primary PCI (pPCI) group ( n=43). The general clinical data, and the parameters of routine echocardiography at 1 day after PCI and before discharge were compared between the two groups. Myocardial contrast echocardiography (MCE) was used to evaluate myocardial perfusion at 1 day after PCI and before discharge. Results:There were no significant differences in general clinical data between the early PCI following thrombolysis group and the pPCI group (all P>0.05). The left ventricular ejection fraction (LVEF) in the early PCI following thrombolysis group and pPCI group before discharge was significantly higher than that on the 1st day after PCI(both P<0.05). The difference of LVEF was significant between the early PCI following thrombolysis group and the pPCI group before discharge and 1 day after PCI ( P<0.05). Compared with 1 day after PCI, the global longitudinal strain (LVGLS) of left ventricle increased in early PCI following thrombolysis group and pPCI group before discharge(both P<0.05). The difference of LVGLS between early PCI following thrombolysis group and pPCI group before discharge and 1 day after discharge was statistically significant( P<0.05). There were no significant differences in left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial volume (LAV), ratio of mitral early diastolic velocity to late diastolic velocity (E/A), mean early diastolic velocity of mitral annulus (Em) and E/Em 1 day after PCI and before discharge between early PCI following thrombolysis group and pPCI group (all P>0.05). MCE showed that the MCE score index of early PCI following thrombolysis group and pPCI group before discharge was significantly lower than that of 1 day after PCI(both P<0.001). Compared to the 1 day after PCI, the early PCI following thrombolysis group showed a significant increase in the proportion of normal microvascular perfusion (nMVP) and a decrease in the proportion of delayed microvascular perfusion (dMVP) and microvascular obstruction (MVO) before discharge (all P<0.05). In contrast, the pPCI group demonstrated a significant decrease in the proportion of both nMVP and dMVP before discharge compared to the first day after PCI (all P<0.05). However, the decrease in the proportion of MVO was not statistically significant ( P>0.05). Conclusions:Early PCI following thrombolysis and pPCI can enhance left ventricular systolic function and myocardial perfusion in patients with acute ST-elevation myocardial infarction. Early PCI following thrombolysis may offer additional advantages in improving left ventricular systolic function and myocardial perfusion.

Objective To evaluate the role of protein kinase Ca (PKCα) in electroacupuncture (EA)-induced reduction of acute kidney injury (AKI) induced by endotoxic shock,and the relationship with nuclear factor E2-related factor 2/heme oxygenase-1 Nrf2/HO-1 pathway in rabbits.Methods Eighty heahhy male New Zealand white rabbits,aged 2 months,weighing 1.5-2.0 kg,were randomly divided into 8 groups (n=10 each) using a random number table:sham operation group (group S),group AKI,specific PKCα inhibitor chelerythrine + AKI group (group CHA),chelerythrine group (group Che),dimethyl sulfoxide (DMSO) group (group D),EA at acupoints + AKI group (group EA),EA at non-acupoints + AKI group (group SEA),and EA at acupoints + chelerythrine + AKI group (group CEA).Bilateral 30 min EA (disperse-dense wave,wave length 0.2-0.6 ms,frequency 2/15 Hz,intensity 1-2 mA) stimulation of Zusanli and Shenshu acupoints was performed once a day for 4 days before establishment of the model and during the process of establishment of the model in EA and CEA groups.In group SEA,EA was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenshu with the same parameters.The animals were anesthetized with iv 20％ urethane 5 ml/kg,tracheostomized and kept spontaneous breathing.Lipopolysaccharide 5 mg/kg (in 2 ml of normal saline) was injected via the auricular vein to establish the model of endotoxic shock-induced AKI in AKI,CHA,EA,SEA and CEA groups,while the equal volume of normal saline was given in S,Che and D groups.At 30 min before establishment of the model,chelerythrine 5 mg/kg (in 0.5 ml of 1％ DMSO) was injected intravenously in CHA and CEA groups,the equal volume of chelerythrine was given in Che group,while the equal volume of DMSO was given in group D.At 6 h after lipopolysaccharide or normal saline injection,blood samples were taken from the internal carotid artery for determination of serum urea nitrogen (BUN) and creatinine (Cr) concentrations.The rabbits were then sacrificed by exsanguinations.The kidney specimens were removed for microscopic examination of pathologic changes which were scored and for determination of superoxide dismutase (SOD) activities,malondialdehyde (MDA) contents,and expression of PKCα protein and HO-1 protein,and expression of Nrf2 in nucleoprotein and total protein.Results Compared with group S,the serum BUN and Cr concentrations were significantly increased,MDA contents were increased,the activities of SOD were decreased,the kidney injury scores were increased,and the expression of PKCα protein,HO-1 protein,and Nrf2 in nucleoprotein and total protein was up-regulated in AKI,CHA,EA,SEA and CEA groups.Compared with group AKI,the serum BUN and Cr concentrations were significantly decreased,MDA contents were decreased,the activities of SOD were increased,the kidney injury scores were decreased,and the expression of PKCα protein,HO-1 protein,and Nrf2 in nucleoprotein and total protein was up-regulated in group EA,and the serum BUN and Cr concentrations were significantly increased,MDA contents were increased,the activities of SOD were decreased,the kidney injury scores were increased,and the expression of PKCα protein,HO-1 protein,and Nrf2 in nucleoprotein and total protein was down-regulated in CHA and CEA groups.The serum BUN and Cr concentrations were significantly higher,MDA contents were higher,the activities of SOD were lower,the kidney injury scores were higher,and the expression of PKCα protein,HO-1 protein,and Nrf2 in nucleoprotein and total protein was lower in group CEA than in group EA,and in CHA group than in CEA group.Conclusion PKCα mediates reduction of endotoxic shock-induced AKI by EA of Zusanli and Shenshu acupoints in rabbits,and the mechanism may be related to activation of Nrf2/HO-1.

Objective To investigate the effect of electro-acupuncture (EA) on nuclear factor E2-related factor 2 (Nrf2) expression in the renal tissues of rabbits with endotoxic shock-induced acute kidney injury (AKI) and the relationship with p38 mitogen-activated protein kinase (p38MAPK) signaling pathway.Methods Seventy male New Zealand white rabbits,weighing 1.5-2.0 kg,aged 2 months,were randomized into 7 groups (n =10 each) using a random number table:normal control group (C group),endotoxic shock-induced AKI group (AKI group),EA + endotoxic shock-induced AKI group (EA group),non-acupoints + endotoxic shock-induced AKI group (SA group),EA + endotoxic shock-induced AKI + specific p38MAPK blocker SB203580 group (EAS group),SB203580 group (S group),and ethanol group (A group).EA (intensity 1-2 mA,frequency 2/100 Hz,wave length 0.2-0.6 ms) of Zusanli and Shenyu lasting for 15 min was performed once a day for 5 consecutive days in EA and EAS groups.In SA group,EA was performed at the points 0.5 cm lateral to the acupoints of bilateral Zusanli and Shenyu using the parameters of EA mentioned above.At 24 h after the last EA,endotoxic shock-induced AKI was induced by injection of lipopolysaccharide (LPS) 5 mg/kg (in 2 ml normal saline) in AKI,EA,SA and EAS groups,while the equal volume of normal saline was given in the other groups.At 30 min before the model was established,5/μmol/kg SB203580 (in 0.5 ml ethanol) was injected intravenously in EAS and S groups,while ethanol 0.5 ml was given in A group and the equal volume of normal saline was given in the other groups.Blood samples were obtained at 6 h after administration of LPS or normal saline for determination of serum urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were sacrificed and kidney specimens were obtained for microscopic examination of pathological changes which were scored and for measurement of Nrf2 protein expression and phosphorylation of p38MAPK (by Western blot) and Nrf2 mRNA expression (using fluorescent quantitative PCR).Results Compared with C group,the pathological score and serum BUN and Cr concentrations were significantly increased,and Nrf2 mRNA and protein expression was up-regulated in AKI,EA,SA and EAS groups,the phosphorylation of p38MAPK was increased in AKI,EA and SA groups,and no significant changes were found in the parameters mentioned above in S and A groups.Compared with AKI group,the pathological score and serum BUN and Cr concentrations were significantly decreased,and Nrf2 mRNA and protein expression was up-regulated in EA and EAS groups,the phosphorylation of p38MAPK was increased in EA group,the phosphorylation of p38MAPK was decreased in EAS group,and no significant changes were found in the parameters mentioned above in SA group.Compared with EA group,the pathological score and serum BUN and Cr concentrations were significantly increased,Nrf2 mRNA and protein expression was down-regulated,and the phosphorylation of p38MAPK was decreased in EAS group.Conclusion The mechanism by which EA mitigates endotoxic shock-induced AKI may be related to activation of p38MAPK signaling pathway and up-regulation of Nrf2 expression in renal tissues of rabbits.

ObjectiveTo evaluate the role of p38MAPK signaling pathway in the up-regulation of heme oxygenase-1 (HO-1) expression in the lung tissue in rats with acute lung injury (AL1) induced by endotoxic shock.MethodsForty-eight male SD rats,aged 8 weeks,weighing 180-200 g,were randomly divided into 4 groups ( n =12 each):control group ( group C ) ; endotoxic shock group ( group LS );endotoxic shock +SB203580 (a specific p38MAPK inhibitor) group (group LSS) and SB203580 group (group SB).Normal saline 0.5ml was injected via the femoral vein in groups C and SB,while LPS 10 mg/kg (in 0.5 ml normal saline) was injected via the femoral vein in groups LS and LSS.When MAP was decreased to 75％ of baseline value,10％ dimethyl sulfoxide (DMSO) 0.1 ml was infused via the femoral vein in groups C and LS,while SB203580 5 mol/kg (in 10％ DMSO 0.1 ml) was infused via the femoral vein at a rate of 0.01 ml/min in groups LSS and SB.Arterial blood samples were obtained at 6 h after LPS or normal saline was given for blood gas analysis and oxygenation index (PaO2/FiO2) was calculated.Then the rats were sacrificed and the lungs were removed for microscopic examination.The pathological changes of the lung were scored.The lung water content was calculated.The MDA content,SOD activity,and expression of HO-1 mRNA and protein,p38MAPK protein and phospharylated p38MAPK (p-p38MAPK) protein were determined.ResultsCompared with group C,the oxygenation index and SOD activity were significantly decreased,the pathological score,lung water content and MDA content were significantly increased,and the expression of HO-1 mRNA and protein and p-p38MAPK protein was significantly up-regulated ( P＜0.05),while no significant change was found in p38MAPK protein expression in groups LS and LSS,and no significant change was found in the indexes mentioned above in group SB (P＞0.05).Compared with group LS,the oxygenation index and SOD activity were significantly increased,the pathological score,lung water content and MDA content were significantly decreased,the expression of HO-1 mRNA and protein was significantly up-regulated,and p-p38MAPK protein expression was down-regulated ( P＜0.05),and no significant change was found in p38MAPK protein expression in group LSS ( P＞0.05).ConclusionThe inhibition of p38MAPK signaling pathway can lead to the up-regulation of HO-1 expression in lung tissues in rats with ALI induced by endotoxic shock.

Objective To evaluate the role of activator protein-1 (AP-1) in the up-regulation of heme oxygenase-1 (HO-1) expression during lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats.Methods Forty-eight healthy male Sprague-Dawley rats,weighing 200-220 g,aged 2.5-3.0 months,were randomly divided into 4 groups (n=12 each): normal control group (group C),ALI group,curcumin + ALI group (group Cur+ ALI),and curcumin group (group Cur).In groups C and ALI,normal saline 0.5 ml and LPS 10 mg/kg (0.5 ml) were injected intravenously,respectively,30 min after 0.1％ dimethyl sulfoxide (the vehicle for curcumin) 0.5 ml was injected intraperitoneally.In groups Cur+ ALl and Cur,curcumin 20 mg/kg (0.5 ml) was injected intraperitoneally,and 30 min later LPS 10 mg/kg and normal saline 0.5 ml were injected,respectively.The rats were then sacrificed at 6 h after injection of LPS.The lungs were removed for microscopic examination.The pathological changes of the lung were scored.The malondialdehyde (MDA) content,superoxide dismutase (SOD)activity and expression of HO-1,AP-1 and HO-1 mRNA in lung tissues were determined.Results Compared with group C,the pathological score and MDA content were significantly increased,the SOD activity was significantly decreased,and the expression of HO-1,AP-1 and HO-1 mRNA was up-regulated in groups ALl and Cur +AL(l) (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group Cur (P ＞ 0.05).The pathological score and MDA content were significantly higher,and the SOD activity and expression of HO-1,AP-1 and HO-1 mRNA were significantly lower in group Cur + ALl than in group ALI(P ＜ 0.05).Conclusion Transcription factor AP-1 activation is involved in the up-regulation of HO-1 expression during LPS-induced ALI in rats.

Objective To evaluate the effect on the reversal of left ventricular aneurysm (LVA) and on heart function of percutaneous coronary intervention (PCI) therapy at different time of acute myocardial infarction (AMI). Methods A total of 326 patients with primary anterior AMI-accompanied LVA diagnosed by left ventriculography (LVG) from January 2001 to July 2004 were enrolled in this study. They were randomized into 4 groups according to the time of accepting PCI:≤3 h group, 4-6 h group, 7-12 h group and one week group. At the baseline and 6 months after AMI, the parameters of left ventricular diastolic volume index (LVEDVI), left ventricular systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), left ventricular wall motion score (LVWMS) and left ventricular end diastolic pressure (LVEDP) were measured by LVG. The paradox volume index (PVI) was measured by equilibrium radionuclide at one week and 6 months after AMI.At 3 year following up to, the major adverse cardiac events (MACE) were recorded. Results At 6 months after PCI, the LVESVI, LVEDVI, WMS and LVEDP were all decreased while LVEF was increased in the four groups as compared with pre-PCl (P<0.05, respectively). Those parameters changed most obviously in ≤3 h group. At the 6th month after PCI, the PVI was lower in ≤3 h group (12.1±2.1)% than in 4-6 h, 7-12 h and one week group [(15.4±2.4)%, (16.5±2.5)% and (20.4±3.7)%, all P<0.05]. Within the 3 years follow-up, the MACE was significantly lower in 3 h, 4-6 h and 7-12 h groups than in one week group, and the mortality was lower too [(2.8%, 3.0% and 3.1% vs. 17.9%, all P<0.05]. Conclusions The early, fully and permanent open of the infraction-related artery can effectively inhibit the left ventricular remodeling process, prevent LVA formation, improve LV function and prognosis.

Objective: To evaluate the influence of recombinant human brain natriuretic peptide(rhBNP)on ventricular remodeling and ventricular systolic synchrony in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).Methods: A total of 48 patients with AMI after PCI were randomized into two groups: rhBNP Group (n=25) and Routine treatment Group (n=23).Two dimension echocardiography was used to measure the index of left ventricular end-diastolic volume (LVEDVI), the index of left ventricular end-systolic volume (LVESVI), left ventricular ejection fraction (LVEF), the index of left ventricular mass (LVMI), the movement index of infarcted regional wall (RWMI) at 1 week, 4 weeks and 24 weeks after the treatment procedure.And at 1 week and 24 weeks period, equilibrium radionuclide angiography was performed respectively to evaluate the ventricular systolic synchrony.Results: ①1 week after PCI, LVESVI in rhBNP group was decreased and LVEF was increased than that in Routine treatment group (P<0.05, respectively).4 and 24 weeks after PCI, LVEDVI, LVESVI, LVEF were significantly different in rhBNP group than those in Routine treatment group (P<0.05,respectively).24 weeks after PCI, RWMI and LVMI were significantly decreased in rhBNP group than those in Routine treatment group(P<0.05,respectively).②24 weeks after PCI, phase shift, full width at half maximum and peak phase standard deviation were significantly improved in rhBNP group than those in Routine treatment group (P<0.05, respectively).Conclusion: Intravenous injection of rhBNP could inhibit left ventricular remodeling and improve left ventricular function.